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In vivo analysis of molecular mechanism of lymphocyte migration in Peyer's patch

派尔氏淋巴结淋巴细胞迁移分子机制的体内分析

基本信息

批准号：
06454265
负责人：
MIURA Soichiro
金额：
$ 3.65万
依托单位：
Keio University, School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

Gut associated lymphoid tissue (GALT) plays an important role for intestinal mucosal defense against dietary and bacterial antigens. In this study, we have established an observatory system of lymphocyte migration in rat Peyer's patches using intravital fluorescence microscopy. Fluorescence labeled lymphocytes adhered to the postcapillary venules (PCV) of Peyer's patches after transient rolling along venular walls. Lymphocytes sticking to the venules increased in number at 10-20 minutes, with preferential adherence of CD4+ cells to venules of 25-50 mum and adherence of B cells to the venules of a wider size range. In this sticking process, adhesion molecules, alpha4-intgerin, L-selectin and CD18/ICAM-1 are shown to be involved. Especially we demonstrated that alpha4-integrin molecule plays a critical role in the early stages of T lymphocyte migration in Peyer's patches. After 30 min, lymphocytes started to extravasate from PCV moved into the interstitium. B cells migrated from venules more quickly than CD4+ cells. Subsequently T lymphocytes preferentially appeared in parafollicular microlymphatics, while few B cells were transported to lymphatics. We also found that alpha4-integrin plays a significant role in the process of transendothelial migration of T lymphocytes in PCV of Peyer's patches. Fat absorption significantly enhanced the rolling and sticking of T cells and subsequent migration into microlymphatics. On the other hand, vasoactive intestinal peptide (VIP) significantly inhibited the transendothelial migration and lymphatic transport without affecting lymphocyte adherence to PCV.By this study, we were able to demonstrate the sequential migration process of lymphocye subpopulations and obtained informations about their regulatory mechanisms.

肠道相关淋巴组织（GALT）在肠道黏膜防御食物抗原和细菌抗原中起重要作用。在本研究中，我们利用活体荧光显微镜建立了大鼠Peyer’s patches淋巴细胞迁移的观察系统。荧光标记淋巴细胞在短暂的沿静脉壁滚动后粘附在Peyer斑块的毛细血管后静脉（PCV）上。在10-20分钟时，淋巴细胞粘附在小静脉上的数量增加，CD4+细胞优先粘附在25-50 mm的小静脉上，B细胞粘附在更大范围的小静脉上。在这个粘附过程中，粘附分子，α 4-整合素，l -选择素和CD18/ICAM-1参与其中。特别是我们证明了α - 4整合素分子在Peyer’s patches中T淋巴细胞迁移的早期阶段起关键作用。30min后，淋巴细胞开始从PCV外渗进入间质。B细胞从小静脉迁移的速度比CD4+细胞快。随后，T淋巴细胞优先出现在滤泡旁微淋巴管中，而少量B细胞被转运到淋巴管中。我们还发现，在Peyer’s patches的PCV中，alpha4-integrin在T淋巴细胞的跨内皮迁移过程中发挥了重要作用。脂肪吸收显著增强T细胞的滚动和粘附，并随后向微淋巴管迁移。另一方面，血管活性肠肽（vasoactive intestinal peptide， VIP）在不影响淋巴细胞粘附PCV的情况下，显著抑制PCV的跨内皮迁移和淋巴运输。通过这项研究，我们能够证明淋巴细胞亚群的顺序迁移过程，并获得有关其调控机制的信息。